2-氟-4-(3-氟-4-甲氧基苯基)苯甲酸 | 1179613-45-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氟-4-(3-氟-4-甲氧基苯基)苯甲酸
• 英文名称: 3,3'-difluoro-4'-methoxy-[1,1'-biphenyl]-4-carboxylic acid
• 英文别名: 2-Fluoro-4-(3-fluoro-4-methoxyphenyl)benzoic acid
• CAS: 1179613-45-6
• 化学式: C₁₄H₁₀F₂O₃
• 分子量: 264.228
• InChiKey: VLFJTOLIFUIBTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氟-4-(3-氟-4-甲氧基苯基)苯甲酸 在 盐酸 、 草酰氯 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  N-Acylethanolamine Hydrolyzing Acid Amidase (NAAA) Inhibitors And Use Thereof

  摘要：

  本文披露了由结构式I表示的化合物：或其药学上可接受的盐。本文描述了结构式I中变量的值。这些化合物可用于调节（例如抑制）N-酰基乙醇胺水解酸酰胺酶（NAAA），从而治疗由NAAA介导的各种疾病、障碍和病症，例如胃肠运动障碍、肠易激综合征、炎症性肠病、神经炎症、尼古丁成瘾、癌症、阿片类药物依赖、止痛、化疗诱导的神经病理性疼痛和疼痛。本文还披露了包括结构式I中的化合物或其药学上可接受的盐的组合物和方法。

  公开号：

  US20190345132A1
• 作为产物：
  描述：

  4-溴-2-氟苯甲酸 、 3-氟-4-甲氧基苯硼酸 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三环己基膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 2-氟-4-(3-氟-4-甲氧基苯基)苯甲酸
  参考文献：
  名称：

  Rational Development of 4-Aminopyridyl-Based Inhibitors Targeting Trypanosoma cruzi CYP51 as Anti-Chagas Agents

  摘要：

  A new series of 4-aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) has been developed using structure-based drug design as well as structure-property relationship (SPR) analyses. The screening hit starting point, LP10 (K-D <= 42 nM; EC50 = 0.65 mu M), has been optimized to give the potential leads 14t, 27i, 27q, 27r, and 27t, which have low-nanomolar binding affinity to TcCYR51 and significant activity against T. cruzi amastigotes cultured in human myoblasts (EC50 = 14-18 nM for 27i and 27r). Many of the optimized compounds have improved microsome stability, and most are selective against human CYPs 1A2, 2D6, and 3A4 (<50% inhibition at 1 mu M). A rationale for the improvement in microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of 14t with the Trypanosoma brucei CYP51 (TbCYP51) orthologue has been characterized by X-ray structure analysis.

  DOI：

  10.1021/jm401067s

文献信息

• N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and use thereof
  申请人：Northeastern University

  公开号：US10689357B2

  公开（公告）日：2020-06-23

  Disclosed herein are compounds represented by Structural Formula I: or a pharmaceutically acceptable salt thereof. Values for the variables in Structural Formula I are described herein. The compounds can be used to modulate (e.g., inhibit) N-acylethanolamine hydrolyzing acid amidase (NAAA) and thereby treat a variety of diseases, disorders and conditions mediated by NAAA, such as a gastrointestinal motility disorder, irritable bowel syndrome, an inflammatory bowel disorder, neuroinflammation, nicotine addiction, cancer, opioid dependence, analgesia, chemotherapy-induced neuropathic pain and pain. Also disclosed herein are compositions and methods including compounds of Structural Formula I, or a pharmaceutically acceptable salt thereof.

  本文公开了结构式 I 所代表的化合物： 或其药学上可接受的盐。结构式 I 中各变量的数值已在本文中描述。本发明化合物可用于调节（例如抑制）N-乙酰乙醇胺水解酸酰胺酶（NAAA），从而治疗由NAAA介导的各种疾病、失调和病症，如胃肠道运动障碍、肠易激综合征、炎症性肠病、神经炎症、尼古丁成瘾、癌症、阿片类药物依赖、镇痛、化疗诱导的神经性疼痛和疼痛。本文还公开了包括结构式 I 化合物或其药学上可接受的盐的组合物和方法。
• [EN] N-ACYLETHANOLAMINE HYDROLYZING ACID AMIDASE (NAAA) INHIBITORS AND USE THEREOF<br/>[FR] INHIBITEURS DE NAAA - AMIDASE ACIDE D'HYDROLYSE DE LA N-ACYLÉTHANOLAMINE - ET LEUR UTILISATION
  申请人：UNIV NORTHEASTERN

  公开号：WO2019217977A1

  公开（公告）日：2019-11-14

  Disclosed herein are compounds represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. Values for the variables in Structural Formula I are described herein. The compounds can be used to modulate (e.g, inhibit) N- acylethanolamine hydrolyzing acid amidase (NAAA) and thereby treat a variety of diseases, disorders and conditions mediated by NAAA, such as a gastrointestinal motility disorder, irritable bowel syndrome, an inflammatory bowel disorder, neuroinflammation, nicotine addiction, cancer, opioid dependence, analgesia, chemotherapy-induced neuropathic pain and pain. Also disclosed herein are compositions and methods including compounds of Structural Formula I, or a pharmaceutically acceptable salt thereof
• Rational Development of 4-Aminopyridyl-Based Inhibitors Targeting Trypanosoma cruzi CYP51 as Anti-Chagas Agents
  作者：Jun Yong Choi、Claudia M. Calvet、Shamila S. Gunatilleke、Claudia Ruiz、Michael D. Cameron、James H. McKerrow、Larissa M. Podust、William R. Roush

  DOI：10.1021/jm401067s

  日期：2013.10.10

  A new series of 4-aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) has been developed using structure-based drug design as well as structure-property relationship (SPR) analyses. The screening hit starting point, LP10 (K-D <= 42 nM; EC50 = 0.65 mu M), has been optimized to give the potential leads 14t, 27i, 27q, 27r, and 27t, which have low-nanomolar binding affinity to TcCYR51 and significant activity against T. cruzi amastigotes cultured in human myoblasts (EC50 = 14-18 nM for 27i and 27r). Many of the optimized compounds have improved microsome stability, and most are selective against human CYPs 1A2, 2D6, and 3A4 (<50% inhibition at 1 mu M). A rationale for the improvement in microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of 14t with the Trypanosoma brucei CYP51 (TbCYP51) orthologue has been characterized by X-ray structure analysis.
• N-Acylethanolamine Hydrolyzing Acid Amidase (NAAA) Inhibitors And Use Thereof
  申请人：Northeastern University

  公开号：US20190345132A1

  公开（公告）日：2019-11-14

  Disclosed herein are compounds represented by Structural Formula I: or a pharmaceutically acceptable salt thereof. Values for the variables in Structural Formula I are described herein. The compounds can be used to modulate (e.g., inhibit) N-acylethanolamine hydrolyzing acid amidase (NAAA) and thereby treat a variety of diseases, disorders and conditions mediated by NAAA, such as a gastrointestinal motility disorder, irritable bowel syndrome, an inflammatory bowel disorder, neuroinflammation, nicotine addiction, cancer, opioid dependence, analgesia, chemotherapy-induced neuropathic pain and pain. Also disclosed herein are compositions and methods including compounds of Structural Formula I, or a pharmaceutically acceptable salt thereof.

  本文披露了由结构式I表示的化合物：或其药学上可接受的盐。本文描述了结构式I中变量的值。这些化合物可用于调节（例如抑制）N-酰基乙醇胺水解酸酰胺酶（NAAA），从而治疗由NAAA介导的各种疾病、障碍和病症，例如胃肠运动障碍、肠易激综合征、炎症性肠病、神经炎症、尼古丁成瘾、癌症、阿片类药物依赖、止痛、化疗诱导的神经病理性疼痛和疼痛。本文还披露了包括结构式I中的化合物或其药学上可接受的盐的组合物和方法。